Molecular Biology

, Volume 35, Issue 2, pp 271–283

Novel Type of Signaling Molecules: Protein Kinases Covalently Linked with Ion Channels

Authors

  • L. V. Ryazanova
    • Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School
  • K. S. Pavur
    • Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School
  • A. N. Petrov
    • Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School
  • M. V. Dorovkov
    • Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School
  • A. G. Ryazanov
    • Department of PharmacologyUniversity of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School
Article

DOI: 10.1023/A:1010499720185

Cite this article as:
Ryazanova, L.V., Pavur, K.S., Petrov, A.N. et al. Molecular Biology (2001) 35: 271. doi:10.1023/A:1010499720185

Abstract

Recently we identified a new class of protein kinases with a novel type of catalytic domain structurally and evolutionarily unrelated to the conventional eukaryotic protein kinases. This new class, which we named alpha-kinases, is represented by eukaryotic elongation factor-2 kinase and the Dictyosteliummyosin heavy chain kinases. Here we cloned, sequenced, and analyzed the tissue distribution of five new putative mammalian α-kinases: melanoma α-kinase, kidney α-kinase, heart α-kinase, skeletal muscle α-kinase, and lymphocyte α-kinase. All five are large proteins of more than 1000 amino acids with an α-kinase catalytic domain located in the carboxyterminal part. We expressed the catalytic domain of melanoma α-kinase in Escherichia coli, and found that it autophosphorylates at threonine residues, demonstrating that it is a genuine protein kinase. Unexpectedly, we found that long aminoterminal portions of melanoma and kidney α-kinases represent new members of the TRP ion channel family, which are thought to mediate the capacitative Ca2+entry in nonexcitable mammalian cells. This suggests that melanoma and kidney α-kinases, which represent a novel type of signaling molecule, are involved in the regulation of Ca2+influx in mammalian cells.

alpha-kinasescalcium channelseEF-2 kinaseprotein kinasesTRP channels

Copyright information

© MAIK “Nauka/Interperiodica” 2001